Suggested Guidelines for the Treatment of Mycosis Fungoides in Countries with Limited Resources

The treatment options for mycosis fungoides (MF) have been expanding but unfortunately many of the currently used treatment modalities are unavailable in Egypt and other African/Arab countries. In addition, there is a lack of consensus on the treatment of hypopigmented MF (HMF), which is a frequently encountered variant in our population. We aimed to develop regional treatment guidelines based on the international guidelines but modified to encompass the restricted treatment availability and our institutional experience. Special attention was also given to studies conducted on patients with skin phototype (III-IV). Treatment algorithm was formulated at Ain-Shams cutaneous lymphoma clinic through the collaboration of dermatologists, haematologists, and oncologists. Level of evidence is specified for each treatment option. For HMF, phototherapy is recommended as a first line treatment, while low-dose methotrexate is considered a second line. For early classical MF, we recommend Psoralen-ultraviolet A (PUVA), which is a well-tolerated treatment option in dark phenotype. Addition of either retinoic acid receptor (RAR) agonist and/or methotrexate is recommended as a second line. Total skin electron beam (TSEB) is considered a third-line option. For advanced stage, PUVA plus RAR agonist and/or methotrexate is recommended as first line, TSEB or monochemotherapy is considered a second line option. Polychemotherapy is regarded as a final option. All patients with complete response (CR) enter a maintenance and follow-up schedule. We suggest a practical algorithm for the treatment of MF for patients with dark phenotype living in countries with limited resources.


Introduction
Mycosis fungoides (MF) is the most common type of cutaneous lymphoma. It has an indolent chronic course refractory to various therapies. Typically, MF presents in its early stages with patches and plaques that may progress to tumours, erythroderma, or visceral involvement, with poor prognosis (Supplementary Tables 1-3 show the ISCL/EORTC revision of the classifcation of MF/SS (2007), the histopathologic staging of lymph nodes in MF/SS, and the ISCL/EORTC revision to the staging of MF/SS, respectively) [1][2][3][4]. Of the many MF subtypes, hypopigmented MF (HMF) is of interest due to its high prevalence among the darker skin type of our population. Apparently, the contrast of the hypopigmented patches makes the diagnosis easier; yet, the true prevalence among diferent skin types needs further studies. It is frequently seen in younger age group and is often associated with CD8 + profle with an indolent course and a high recurrence rate [5]. On the other hand, some variants may have an aggressive behavior as follicular MF (FMF) and MF with large cell transformation (LCT). Terefore, treatment options should be tailored according to the clinical and the histopathological features of the disease [6,7].
Management of MF is based on its stage. For early stages, therapies include topical corticosteroids, phototherapy, topical bexarotene, radiotherapy, and nitrogen mustard preparations. While for advanced stages, options include bexarotene, histone deacetylase inhibitors, interferon, antibody therapies, systemic chemotherapy, and allogeneic hematopoietic cell transplantation (HCT) [8].
Many of the current mainstay treatment options for MF, such as bexarotene, extracorporeal photophoresis, interferon, histone deacetylase inhibitors, nitrogen mustard, and biologics are either unavailable or not covered by medical insurance in Egypt and other countries with limited resources [9]. In addition, there is no standardized stepwise approach among diferent specialties in the management of cutaneous lymphoma; certain specialties might use aggressive treatment lines in early stages of the disease which increase the risk of relapse and the mortality rate. Tus, management of MF with adherence to international guidelines represents a major challenge. We therefore present an alternative treatment algorithm for adult patients with MF and patients with HMF of all ages with special consideration to darker skin phototypes, excluding patients with other types of systemic lymphoma if associated. Te presented guidelines are based on our institutional experience and the treatment availability in our country. Tis is formulated to provide a practical guide for dermatologists, haematologists, and oncologists to unify the quality of care in clinics and institutions all over Egypt and to share our experience with other countries with limited resources.

Methods
Treatment approach was based on the literature review for the international guidelines for the treatment of MF as European Organisation for Research and Treatment of Cancer (EORTC), 2017 [10]; European Society for Medical Oncology (ESMO), 2019 [11]; National Comprehensive Cancer Network (NCCN), Version 2 2019 [12] and 2020 [13]; and British Association of Dermatologists and U.K. Cutaneous Lymphoma Group guidelines (BAD-UKCLG), 2018 [14]. Te literature review was done until July 2020 on PubMed, Embase databases, the Cochrane Library for metaanalysis, systemic reviews, randomized and nonrandomized clinical studies, cohort, case-control studies, case series, and case reports of MF and Sezary syndrome (SS) treatment options using specifc search terms shown in (Supplementary Table 4). Special attention was also given to studies conducted on patients with skin phototype (III-IV). Only English articles with available/accessible treatment modalities were included. Tis guideline has been developed with reference to the Appraisal of Guidelines Research and Evaluation (AGREE II) instrument (http://www.agreetrust. org) [15].
Te guideline development group included dermatologists, haematologists, and oncologists at Ain Shams cutaneous lymphoma clinic. Diferent authors were allocated to the appraisal of the literature review of specifc treatment options. Te guideline was discussed among patients attending the cutaneous lymphoma clinic, using previously formulated self-assessment questionnaires, phone calls, and face to face interviews, to gather their opinions regarding the efcacy, cost, feasibility of each treatment, and its efect on their quality of life. Te guideline has been peer reviewed by dermatology consultants with special expertise in the feld of cutaneous lymphoma to assess its usefulness and applicability. Recommendation drafts were sent through e-mails and were circulated to the authors for fnal amendments to be made. Informal consensus was reached through a series of discussions and several e-mail deliberations.
Recommended treatment options are presented as an algorithm according to the disease stage. Patients with specifc variants are discussed separately owing to the variation in their prognosis from classic MF. Dose and treatment duration are provided; and maintenance/follow-up protocol is designed. Level of evidence is specifed for each treatment option using Oxford Centre for Evidence-Based Medicine 2011 (OCEBM) (Supplementary Table 5 shows the details of OCEBM) [16].
Data regarding the response rate, treatment availability, cost, side efects, emerging new drugs, patients' preferences, and quality of life will be collected and registered in the clinic database.
Tis guideline will be reviewed and updated every 5 years if deemed necessary depending on the results of any future studies and collected data.

Treatment Options for Classic MF
3.1.1. Expectant Terapy. Expectant therapy has been recommended by the EORTC for patients with stage IA MF especially those with T1a because they usually show very low risk of progression (10% after 10 years) with normal life expectancy [10,[17][18][19]. However, expectant therapy is not convenient in our community due to lack of some patients' commitment to regular follow-up. In addition, Pavlotsky et al. [20] reported that progression and even rare fatalities may occur in early-stage disease.

Topical Treatment.
Available topical treatment options are listed in Table 1.
(1) Topical Steroids. Topical corticosteroids are widely accepted for treatment of MF, either as monotherapy in stage IA or adjuvant therapy in later stages. Clobetasol propionate cream 0.05% applied twice daily show remission; however, responses are not durable or complete [11,21]. Side efects from prolonged use are minimal [22].
(2) Topical Retinoids. Bexarotene is a retinoid X receptor that is approved by the FDA for the treatment of refractory cutaneous lesions in stage I [23]. Unfortunately, it is not available in Egypt and instead, we use tazarotene 0.1% gel for refractory patches [24]. It has been studied for refractory lesions and shows promising results. It can also be used under occlusion combined with topical steroid ointment [25]. Moreover, in a Canadian study, tazarotene 0.1% cream was used as monotherapy for early patch disease [26]. It is important to mention that like bexarotene, tazarotene is contraindicated during pregnancy.
(3) Topical Chemotherapy. Topical mechlorethamine was approved by the European Medicines Agency (EMA) for the treatment of early-stage MF but it is not available in our country [27]. An interesting in vitro and ex vivo study showed that gentian violet, the widely available inexpensive agent, can act as anticutaneous lymphoma agent through inducing tumour cell apoptosis and blocking its growth [28]. In addition, there is a case report of a patient with recalcitrant, localized patch disease stage IB that showed improvement and reduction of erythema with gentian violet when applied once daily for 2 months [29]. Terefore, we included this agent in our guidelines.
(4) Moisturizers. Moisturizers are used as basic routine care for patients with MF. It is of pivotal importance to maintain the integrity of skin barrier in these patients to guard against infections [30]. Tey may reduce transepidermal water loss and decrease the scaling and itching sensation [31]. Teir role is highlighted in a placebo-controlled study evaluating the purine nucleoside phosphorylase inhibitor (peldesine cream) for the treatment of cutaneous lymphoma. Results showed relatively high (24%) placebo response rate versus (28%) the peldesine group [32].

(5) Other Topical Terapies.
Other studies investigated the use of imiquimod [33,34], tacrolimus [35], and 5fuorouracil [36], and show their benefcial role in the treatment of early MF; however, there is a lack of controlled studies to validate their efcacy; therefore, we did not include them in our guidelines [31].

Phototherapy
(1) Narrow-Band Ultraviolet B (NB-UVB). NB-UVB is the most readily available type of phototherapy in Egypt. It can cause complete remission of patches ranged from 54% to 90% [37,38]. A Tunisian study showed that NB-UVB is efective for the treatment of noninfltrative plaque irrespective of the skin phototype [39]. NB-UVB is administered as 3 sessions per weeks in most of the studies [38]. Studies did not show increased carcinogenesis with NB-UVB [38,40]. Interestingly, patients who have not previously responded to psoralen-ultraviolet A (PUVA) may show improvement with NB-UVB [38,41,42].
(2) Psoralen-Ultraviolet A (PUVA). PUVA is an efective treatment for early MF especially in patients with thick plaques, dark phenotypes, and those refractory to NB-UVB [38,43,44]. It is more efective than NB-UVB in inducing complete clearance [8,45]. Te NCCN [13] and BAD [46] recommend PUVA as a frst line for predominately plaque disease. Durable remission (10 years) can be achieved in 30-50% of patients [47]. Complete response (CR) is achieved in 85% for stage IA, 65% for stage IB, and 85% for stage IIA. Te time to CR is much longer in patients with plaques than patches [38]. An Egyptian study showed that patients respond less to phototherapy and usually need double the number of sessions due to their darker phenotype [48]. PUVA is often prescribed with 8-methoxypsoralen (MOP), that is available in Egypt and given 2-3 times weekly [31]. High cumulative dose of PUVA can lead to photodamage and photocarcinogenesis. Lifetime PUVA exposure should be limited to 1200 J·cm 2 and/or 250 sessions [46]; however, these studies have been performed on patients with fair colour. No studies are available from populations with darker phototypes that are naturally more protected against photodamage.
Regarding the tumour stage, PUVA is given combined with systemic therapy as CR to monotherapy for most of the studies is poor. In erythroderma, CR is achieved in 43%; however, patients only tolerate low doses of PUVA owing to photosensitivity [38].
Bath PUVA is not commonly used and can lead to early relapse as the head is not exposed to treatment. However, it can be reserved for patients with contraindications to oral PUVA. Treatment was given at a dose of 0.2 mg/L 8methoxypsoralen, 3 times weekly followed by UVA irradiation [43,49,50]. Topical PUVA can be given to unilesional MF or pagetoid reticulosis [51].
Studies on phototherapy for MF patients are shown in Table 2.
For decades, climatotherapy has been considered as an established line of treatment for psoriasis. Recently, it has been suggested for other T cell-mediated skin conditions, like mycosis fungoides and atopic dermatitis. Several locations have been suggested as destinations for climatotherapy, including the alpine mountains in Switzerland, the Dead Sea, and certain locations on the Red Sea. Luckily, the latter is available in Safaga, Red Sea, Egypt. Direct exposure to the sun on a regular basis for several days showed some promising results in inducing remission in patch-stage MF. In addition, PUVA-sol has been suggested as an alternative home-based phototherapy in some regions. However, this treatment modality needs to be studied further. It should be considered as a complementary modality rather than a treatment on its own [56,57].

Phototherapy Plus Systemic
Terapy. PUVA can be combined with systemic treatment as interferon and retinoids to increase the efcacy in refractory/advanced cases and to decrease the cumulative dose of UVA, thus, reducing the long-term side efects. According to ESMO guidelines, it is considered as a 1 st line in the advanced stage and a 2 nd line therapy in refractory cases of the early stage [11]. However, sufcient data regarding the efcacy of combined treatment over PUVA monotherapy are lacking [38].
Drugs available in Egypt that can be combined with PUVA are retinoic acid receptor (RAR) agonists and methotrexate.

Dermatology Research and Practice
(1) PUVA and RAR Agonists. RAR agonists include acitretin and isotretinoin. Tomson et al. [58] treated a group of early MF patients with either etretinate or isotretinoin plus PUVA and the other group was treated with PUVA alone. Te response rate did not signifcantly difer between both groups; however, the dose of UVA is much lower in the combined group which decrease the toxicity. In addition, patient showed a prolonged remission when they receive retinoids as a maintenance therapy. In a recent multicentre retrospective study in Greece, acitretin was shown to be more efective when patients concomitantly received PUVA or topical steroids than when patients receiving acitretin alone. Most of the patients were at early stage (92%), and 18% had FMF [59].
(2) Phototherapy and Methotrexate. Te combination of PUVA and methotrexate is not recommended due to the risk of increase carcinogenesis [38]. However, no solid evidence exists regarding this risk especially in populations with darker phenotype. Tis combination has been used in psoriasis and proved its efcacy [60,61] and antiangiogenic efect [62]. Moreover, recent mathematical modeling of cancer cell mutational dynamics hold a new promise for the use of methotrexate in combination with NB-UVB through attacking multiple signaling pathways simultaneously. Tis will decrease cross resistance and provide better disease control [63].

RAR Agonists as a Systemic
Monotherapy. RAR agonists exert a modest activity against MF as a monotherapy with more potent efect when combined with phototherapy [14,59]. In a retrospective study on patients with early MF, 25 patients received acitretin and 12 patients received isotretinoin at a dose of 0.3 mg/kg and 0.2 mg/kg, respectively. Te median treatment duration was 10 months for acitretin, and 9 months for isotretinoin. Te overall response was 64% for acitretin and 80% for isotretinoin, and CR was 4% and 8%, respectively [64].
Cumulative data regarding the use of RAR agonists in MF showed that the overall response rates ranges from 43% to 100% and the median response duration ranges from 3 to 15 months [65]. No controlled studies are available comparing the efcacy of acitretin versus isotretinoin [10]. Nevertheless, a single case report showed the superior effcacy of isotretinoin for the treatment of FMF [66]. According to the NCCN guidelines 2020, acitretin is regarded as an alternative category A systemic treatment and can be used starting stage IIB [13].

Other Combined Systemic Treatments.
Methotrexate enhances the efect of bexarotene [67]. Methotrexate and acitretin have been used before in psoriasis in refractory cases and showed efcacy with no report of increased liver toxicity [68]. However, no enough data exists regarding the combined use of methotrexate and acitretin for MF.

Radiotherapy.
Radiotherapy is considered an important treatment option in the management of patients with MF in both early and advanced stages [69], and can be used for the eradication of unilesional disease or for the palliation of multisite disease. Total skin electron beam (TSEB) may be used for efective palliation, and those patients may often have long-term disease-free intervals [70], but we have to consider that due to the rarity of this disease, there are no randomized trials directly comparing radiotherapy to other treatment options [69]. Protocol of radiotherapy treatment for MF/SS in Egypt is shown in Figure 1.
(1) Radiotherapy in Unilesional Mycosis Fungoides. Radiotherapy can be curative in patients with unilesional MF and CR rates can be as high as 100%, with no recurrences at treated sites [71]. In the few available reports, doses have ranged between 6-40 Gy (usually 1.8 Gy/F) with local recurrence unusual above 24 Gy [70]. Te usual dose used in Ain Shams University ranges between 24 and 30 Gy/F usually using a tissue equivalent bolus (thickness either 0.5 or 1 cm) with 2 cm margin.

(2) Localized Radiotherapy as a Palliative Measure in MF.
Radiotherapy plays a central role in local palliation, particularly for lesions localized in sanctuary areas. Symptomatic cutaneous lesions (as cosmetic disfgurement, itching, scaling, or discharging) and lesions unresponsive to other therapeutic options may be managed with radiotherapy in any stage of MF [72].
Low doses as 4 Gy (2 Gy/F) can be used and allows overlapping felds to treat lesion at any site [69], but response rate is low being <30% and so higher palliative doses (8 Gy or more) are recommended, doses ranging between 8 and 12 Gy allow retreatment of needed lesions [70]. Te usual palliative doses used in Ain Shams University ranges between 10 and 12 Gy (2 Gy/F) using a tissue equivalent bolus as in unilesional treatment but a narrower margin may be used. It is usually given to patient with localized nodules (stage IIB).

(3) Total Skin Electron Beam (TSEB).
Modern TSEB has an overall response rate approaching 100% and remains a fundamental treatment for MF, with no other treatment approaching such a high response rate. However, it is a very complicated treatment requiring a skilled multidisciplinary team, highly experienced in the management of cutaneous lymphoma [73]. Tese technical difculties and the unavailability of radiotherapy unit that is constructed for offering TSEB in Ain Shams University represent the main obstacle in applying TSEB as a routine management of patient with MF and so we usually refer our patient to receive TSEB (whenever indicated) to other radiotherapy units (although limited number of these units in Egypt generally). It is usually given to patients with stage IIB with extensive nodules and as a second line therapy for patients with T2b, stage III and IV.
According to EORTC guidelines [74], TSEB can be used for patients with all stages of MF, and remains a very important treatment for these patients, even for those with SS. Moreover, the recent NCCN guidelines 2020 stated that TSEB can be considered as early as stage IB [13]. Te response rates and duration of response are higher in earlier stage disease. Te aim of treatment (curative or palliative) varies depending on the stage [69]. Te goal of TSEB is to deliver a relatively uniform dose of radiation to the entire skin while limiting acute and long-term toxicities [75].
Te 6-feld large electron feld technique developed at Stanford is the most commonly used [76]. Te patient is treated in six diferent standing positions over the course of 2 treatment days ( Figure 2) [75]. Tis cycle is repeated twice per week [75], the traditional dose used is as high as 36 Gy [74], and still this is our recommended dose in Ain Shams University whenever referring a patient with MF for TSEB.
More recently, lower dose regimens (10-12 Gy) have been investigated and showed their efcacy with the advantage of allowing multiple retreatments and being more convenient for patients [77,78]. However, there are no controlled comparative studies investigating the efcacy of the standard dose versus the low dose TSEB in inducing remission [10].
(4) External Beam Radiotherapy in Metastatic Disease. External beam radiotherapy can be given for patients with nodal or visceral involvement as the standard approach for patients with non-Hodgkin lymphoma in a dose 20-30 Gy (2-3 Gy/F) [14,79].
3.1.8. Chemotherapy. According to NCCN 2020 guidelines, methotrexate ≤50 mg per week is considered as category A systemic treatment for treatment of patients with tumour stage. Category B systemic treatment, which are more toxic include Gemcitabine and pegylated liposomal doxorubicin can be used for patients with advanced stage MF/SS. Multiagent chemotherapy, though efective, are more toxic and associated with higher risk of mortality, so are reserved only for refractory cases or for nodal or visceral metastasis. Tey can also be used as a bridge to allogeneic HCT [13]. Methotrexate can be used from stage IIB, gemcitabine or liposomal doxorubicin can be used from stage IV and polychemotherapy is regarded as a fnal treatment option (Table 3).

Algorithm for Treatment of Classic MF/SS. Te main aim of treatment is to improve the patients' quality of life (QOL).
It is important to mention that the early use of systemic treatment does not lead to a better outcome than using skindirected therapy (SDT) [83]. Terefore, treatment options are presented in a stepwise pattern as the main objective of the treatment is to control the patients' disease with minimal toxicity. Terefore, SDT is given as a frontline in patients with early classic MF, while systemic and combined therapy is reserved for the late cases and transformed MF (Figure 3). Monochemotherapy can also be considered for early cases refractory to SDT and other systemic therapies, to decrease the tumour burden and improve the QOL.
Putting patients' feedback into consideration, NB-UVB can be given instead of PUVA if the latter is inaccessible. Moreover, some patients complained of the unavailability of nearby phototherapy units as in rural areas, we suggest shifting to second line in the treatment algorithm as an alternative.

Hypopigmented MF (HMF). Hypopigmented MF (HMF)
is the most common variant of MF in children [84][85][86]. It is common in the Arab population and dark-skinned individuals. Patients usually have other types of MF lesions [87]. Reported treatment includes NB-UVB, PUVA, topical steroids, topical bexarotene, topical tazarotene, and topical carmustine. Phototherapy is the most commonly used treatment and is usually combined with topical steroids Radiotherapy [8,30] Definitive role Local RT [69,70] Unilesional (IA, IIA) [ [88][89][90]. PUVA ofers greater response and longer remission than NB-UVB [91][92][93]. Recurrence is common and maintenance PUVA showed lower rate of relapse compared to patients not receiving maintenance treatment [88]. Topical bexarotene and tazarotene are the most common used topical retinoids. Systemic treatment as systemic retinoids and methotrexate has been investigated in adults but there are no sufcient data regarding their use in children [86]. No progression to advanced stage has been noticed [85,86,89,94]; however, Amorim et al. [95] reported progression in some cases. Te British Phototherapy Group does not recommend PUVA for children less than 10 years old [96]. Accordingly, phototherapy is recommended as a frst line treatment in our institute for HMF (Level 4), where NB-UVB is given to children less than 10 years and PUVA is the preferred treatment modality for patients older than 10 years (level 3). Moisturizers and mid potent steroid are basic treatment for all patients (level 5). Low-dose methotrexate is only reserved for recalcitrant cases (level 5) (Figure 4).

Follicular MF (FMF).
In general, SDT is insufcient to control FMF and multiple systemic therapies are needed [6]. However, it is crucial to diferentiate between the indolent   Dermatology Research and Practice early variant and the aggressive advanced variant of FMF [97]. In a single-institution retrospective study, acitretin is used in combination with either radiotherapy or interferon in the treatment of FMF and then continued alone for maintenance [98]. In a case report, 0.1% tazarotene gel and a layer of 0.1% triamcinolone ointment under occlusion were used for resistant lesion of FMF and showed good response [25].
According to NCCN 2020 guidelines, patient with early FMF can be treated with SDT, while those with advanced stage can be treated with category A systemic treatment as methotrexate or acitretin before considering category B systemic treatment as monochemotherapy [13]. Tis is in agreement with the report of the Dutch cutaneous lymphoma group and other studies that recommend SDT for early FMF cases, while late cases are treated with more   10 Dermatology Research and Practice intensive treatment [99][100][101]. Usually, PUVA for early FMF needs longer induction phase [101]. We adhere to the previous regimen in managing FMF (Level 3) ( Figure 5).

MF with Large Cell Transformation (LCT).
Large cell transformation (LCT) is diagnosed when large cells constitute more than 25% of lymphoid infltrates in a skin lesion biopsy. CD30 expression is found in 30% to 50% of transformed cases and these patients may beneft from CD30-directed therapies [8,102,103]. However, brentuximab vedotin (anti-CD30) is rarely used in Egypt because it is very expensive and not covered by medical insurance. MF with LCT is often aggressive and requires systemic treatment (liposomal doxorubicin, pralatrexate, gemcitabine, and romidepsin) [13,104]. In a single case report, CD30-negative transformed MF showed good response to treatment with bexarotene and methotrexate [105]. Unfortunately, most of the abovementioned treatments are unavailable.
Accordingly, monochemotherapy (Level 4) as gemcitabine [106] or liposomal doxorubicin [107] can be given in our institute to generalized disease with or without skindirected therapies [13,102]. For localized LCT (i.e., restricted to one or few nodules/plaques), localized radiotherapy can be used alone along with the other treatment modalities used before transformation. Polychemotherapy is regarded for refractory cases ( Figure 6) [13].

Maintenance Terapy and Follow-Up Schedule.
Tough previous reports did not show solid evidence for the use of maintenance therapy with phototherapy [108], a multicentre prospective randomized clinical trial with lowdose, low-frequency PUVA maintenance regimens showed prolonged median disease-free remission. Patients with CR were randomized to receive PUVA maintenance for 9 months. Tis prolongs the median disease-free remission from 4 months to 15 months (Level 2) [109]. Maintenance NB-UVB can also prolong the remission in the early stage [110]. Moreover, in a recent review, maintenance therapy was found to be necessary in most of the cases [111].
According to the guidelines for phototherapy of MF/SS of the United States Cutaneous Lymphoma Consortium (US CLC) [38], maintenance therapy by either NB-UVB or PUVA is given to induce prolonged remission of therapy in MF patients that have potential risk of decreased survival. Tey defned three phases of phototherapy: induction, consolidation, and maintenance phases. Induction phase represents the time from the start of phototherapy till CR is achieved. Consolidation phase lasts for 1-3 months after CR. Maintenance phase follows the consolidation phases till discontinuation of therapy ( Figure 7). Accordingly, we follow these US CLC guidelines. Recommendations for the UV doses and the frequency of sessions during the induction and maintenance phases are included in (Supplementary  Table 6

Dermatology Research and Practice
For advanced MF/SS, salvage PUVA therapy can be used after systemic therapy [31]. Other reported maintenance therapies include low-dose methotrexate, acitretin, tazarotene, and topical steroids (level 5) [10].
Follow-up is recommended every month during induction, consolidation, and maintenance stages, then every 3 months afterwards.

Conclusion
We suggest a practical algorithm for the treatment of MF in patients with darker phenotype, in adherence with the international guidelines and in the context of limited medical resources.

Data Availability
Te data supporting these guidelines are from previously reported studies, which have been cited. Te processed data include questionnaires from the patients that are available from the corresponding author upon request.

Conflicts of Interest
Te authors declare that they have no conficts of interest.

Supplementary Materials
Supplementary  Figure 7: Maintenance regimen with phototherapy. Treatment of MF patients with phototherapy includes 3 phases: induction, consolidation, and maintenance. Te dose of UV is escalated during the induction phase with fxation of the frequency of sessions, while both the dose and the frequency are fxed during the consolidation phase. During the maintenance phase, there is a gradual decrease of the frequency of the sessions with fxation of the dose [38]. * Complete response is determined clinically, and has to be ≥ 4 weeks; biopsy is only required when assessing postinfammatory hyperpigmentation or erythema versus the presence of residual lesion [112].